As the prior method for producing an acetylene compound of formula (3), there is known a method in which 4-nitrophenol (compound (5)) is reacted with 2-methyl-3-butyn-2-chloride (compound (6)) in the presence of a base (see, for example J. Med. Chem., 1983, vol. 26, No. 11, p. 1582 and JP-A-58-188880).
It is also reported a method in which 4-nitrophenol (compound (5)) is reacted with 2-methyl-3-butyn-2-chloride (compound (6), in the presence of copper iodide catalyst, potassium iodide and potassium carbonate (see, for example Synthesis, 1995, vol. 6, p. 707).
Also, it is reported a method in which 4-nitrophenol (compound (5)) is reacted with a derivative of 2-methyl-3-butyn-2-ol (compound (7)) in the presence of copper catalyst and DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) (see, for example Tetrahedron Lett., 1994, vol. 35, p. 6405).
In addition, it is reported a method in which 4-nitrophenol (compound (5)) is reacted with 2-methyl-3-butyn-2-ol in the presence of triphenylphosphine and DEAD (diethyl azodicarboxylate) (Mitsunobu Reaction, see, for example Synth. Commun., 1989, vol. 19, p. 1255).
As the preparing method by using 4-nitrofluorobenzene as a raw material, there is known a method in which 2-methyl-3-butyn-2-ol is used instead of a solvent, and the raw material is reacted with potassium alkoxide of 2-methyl-3-butyn-2-ol (see, for example J. Org. Chem., 1972, vol. 37, p. 841).
(wherein X means Cl, —OCO2CH3 or —OCOCF3.)
The preparing method described in J. Med. Chem., 1983, vol. 26, No. 11, p. 1582, and JP-A-58-188880 has some problems, such as a low yield, the use of 2-methyl-3-butyn-2-chloride (compound (6)) being relatively unstable.
Although the preparing method described in Synthesis, 1995, vol. 6, p. 707 gives an improved yield of 89% by using copper catalyst, it has some problems, such as removal of the copper catalyst being heavy metal, and the use of a large amount of potassium iodide that is not necessarily said to be inexpensive in case where potassium iodide is used, and the like. In addition, a problem regarding the stability of 2-methyl-3-butyn-2-chloride remains. Further, there is problems in the aspects of procedure ability and cost, such as the use of 2-methyl-3-butyn-2-chloride in an amount of 2 times molar of 4-nitrophenol (compound (5)).
The preparing method described in Tetrahedron Lett., 1994, vol. 35, p. 6405 is similar to the above-mentioned method, but the yield is 81% at most in case where 2-methyl-3-butyn-2-chloride is used, the use of trifluoroacetate that gives the highest yield (88%) is clearly disadvantageous in the aspect of cost, and DBU used is also expensive. Therefore, this method is not suitable as an industrial preparing method.
Also, the preparing method described in Synth. Commun, 1989, vol. 19, p. 1255 is not suitable as an industrial preparing method from viewpoint of low yield (45%) and the cost of expensive DEAD or the like.
The preparing method described in J. Org. Chem., 1972, vol. 37, p. 841 can be said to be a preparing method excellent in the cost and procedure ability as it use 2-methyl-3-butyn-2-ol and 4-nitrofluorobenzene as raw materials that are relatively inexpensive and stable, and it does not use catalysts such as heavy metal. However, this method has problems such as low yield of 35%, long reaction time (room temperature, 3 days) or the like.